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total saponins of panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage

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Chinese Journal of Integrative Medicine 2022年第5期28卷 410-418页

作者： PAN Yu-wei WU Dong-ping LIANG Hua-feng TANG Gen-yun FAN Chun-lin SHI Lei YE Wen-cai LI Man-mei JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research Jinan UniversityGuangzhou(510632)China Department of TCM Preventive Medicine Tianhe District Hospital of Traditional Chinese MedicineGuangzhou(510632)China Institute of Traditional Chinese Medicine and Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollege of PharmacyJinan UniversityGuangzhou(510632)China

Objective:To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of panax notoginseng saponins(TSPN)on cerebral ischemia-reperfusion injury and oxygenglucose deprivation/reoxygenation(OGD/R)of cultured cortical ***:The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay,flow cytometry and live/dead cell *** morphology of dendrites was detected by *** cerebral artery occlusion(MCAO)was developed in rats as a model of cerebral *** neuroprotective effect of TSPN was evaluated by neurological scoring,tail suspension test,2,3,5-triphenyltetrazolium chloride(TTC)and Nissl *** blot analysis,immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin(mTOR)signaling ***:MTT showed that TSPN(50,25 and 12.5μg/m L)protected cortical neurons after OGD/R treatment(P<0.01 or P<0.05).Flow cytometry and live/dead cell assays indicated that 25μg/m L TSPN decreased neuronal apoptosis(P<0.05),and immunofluorescence showed that 25μg/m L TSPN restored the dendritic morphology of damaged neurons(P<0.05).Moreover,12.5μg/m L TSPN downregulated the expression of Beclin-1,Cleaved-caspase 3 and LC3 B-Ⅱ/LC3 B-Ⅰ,and upregulated the levels of phosphorylated(p)-Akt and p-mTOR(P<0.01 or P<0.05).In the MCAO model,50μg/m L TSPN improved defective neurological behavior and reduced infarct volume(P<0.05).Moreover,the expression of Beclin-1 and LC3 B in cerebral ischemic penumbra was downregulated after 50μg/m L TSPN treatment,whereas the p-mTOR level was upregulated(P<0.05 or P<0.01).Conclusions:TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal *** promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage,

关键词： total saponins of panax notoginseng oxygen-glucose deprivation and reoxygenation neuroprotection ischemia-reperfusion Akt/mTOR pathway Chinese medicine

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Effects of total saponins of panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

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Neural Regeneration Research 2015年第9期10卷 1450-1456页

作者： Xu He Feng-jun Deng Jin-wen Ge Xiao-xin Yan Ai-hua Pan Zhi-yuan Li Department of Anatomy and Neurobiology School of Basic Medical Sciences Central South University Department of Anatomy Yiyang Medical College Department of Pharmacy Yiyang Medical College Department of Integrated Traditional and Western Medicine Hunan University of Traditional Chinese Medicine

The main active components extracted from panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. total saponins of panax notoginseng enhanced the number of dou- blecortin （DCX）＋ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX＋ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of panax notoginseng promote differentiation of DCX＋ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.

关键词： nerve regeneration total saponins of panax notoginseng cerebral ischemia/reperfusion immature neurons neurogenesis doublecortin olfactory bulb neural regeneration

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Effects and mechanisms of total saponins of panax notoginseng on the transdifferentiation of human renal tubular epithelial cells mduced by aristolochic acid Ⅰ

Effects and mechanisms of total saponins of panax notoginsen...

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2008北京国际生理科学学术大会

作者： XU Ya-Ji PAN Qiang-Wen FENG Zhi-Qiang* Department of Physiology Luzhou Medical College Luzhou 646000 China

＜正＞Objective:Aristolochic acid nephropathy（AAN） is a renal disease reported after the introduction of Chinese herbs contained aristolochic acid.A great quantity studies suggest that tubular epithelial-myofibroblast transdifferentiation（TEMT） induced by aristolochic acid（AA） may be the prominent reason of renal interstitial *** saponins of panax notoginseng（PNS） can prevent the development of liver and renal *** objective of our experiment is to observe whether PNS can inhibit AA I triggered TEMT and its mechanism,and to provide a new scientific foundation of blocking chronic aristolochic acid ***:HK-2 cells were divided into 6 groups,including negative control group,PNS control group,AA I induced group and PNS treated group with different doses（200,400,600μg/mL）.Each group was cultured for 48 h in *** morphological change of cultured tubular cells was observed by inverted phase contrast microscopy;the expression ofα-SMA was assessed by immunohistochemistry;the content of TGF-β1 in the culture supernatant was measured by ELISA;the level of CTGF mRNA was evaluated by ***:AA I caused transdifferentiation of HK-2 cells to myofibroblast-like cells and showed strongα-SMA expression,the IOD value ofα-SMA expression was more than that of negative control group,the content of TGF-β1 in supernatant and the level of CTGF mRNA were also increased（P＜0.05）.The morphological change of HK-2 cells was decreased in PNS treated groups with different doses,PNS inhibited the expression ofα-SMA,CTGF mRNA and TGF-β1 in a dose-dependent manner （P＜0.05）.There was no difference in the measured indexes between PNS control group and negative control ***:AA I can increase the content of TGF-β1 and the level of CTGF mRNA,thus increase the expression ofα-SMA and induce TEMT;TEMT andα-SMA expression are down-regulated by PNS in a dosedependent manner,the negative regulation of PNS may be partially achieved by attenuation of TGF-β1

关键词： total saponins of panax notoginseng transdifferentiation α-smooth muscle actin connective tissue growth factor

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Attenuation of Brain Inflammatory Response after Focal Cerebral Ischemia/Reperfusion with Xuesaitong Injection (血塞通注射液) in Rats

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Chinese Journal of Integrative Medicine 2006年第3期12卷 203-206页

作者：何蔚徐小军 Department of Pharmacology Gannan Medical CollegeJiangxi (341000) Department of Pharmacy Affiliated Hospital of Gannan Medical College

Objective： To investigate the neuro-protective effect of Xuesaitong Injection （血塞通注射液, XST） on brain inflammatory response after transient focal cerebral ischemia/reperfusion in rats. Methods： Focal cerebral ischemia/reperfusion models of male rats were induced by transient occlusion for 2 h of middle cerebral artery （MCA） which was followed by 24 h reperfusion. XST was administered through intraperitoneal injection of 25 mg/kg or 50 mg/kg at 4 h after the onset of ischemia. After reperfusion for 24 h, the neurological function score was evaluated, the brain edema was detected with dry-wet weight method, the myeloperoxidase （MPO） activity and the expression of intercellular adhesion molecule-1 （IOAM-l） of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively. Results： XST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and IOAM-1 expression as compared with the ischemia/reperfusion model group （P〈0.01）. Conclusion： XST has a definite effect on inhibiting the expression of IOAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.

关键词： Xuesaitong Injection total saponins of panax notoginseng cerebral ischemia brain injury neutrophil intercellular adhesion molecule-1

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